Biomedical subjects

S C Choi

Publications and source records attributed to S C Choi.

At least 37 records · Page 2Linked to original sources

PubMed1999

Fractal dimension calculated from two types of region of interest.

OBJECTIVES: To compare the effect of using two region of interest (ROI) types on calculating the fractal dimensions of trabecular bone during simulated osteoporosis. METHODS: Ten 5 mm thick cross-sections from the long bone of a cow were progressively decalcified in 0.1 N Hcl for 5, 10, 20, 30, 60 and 90 min intervals, and radiographed using 0 degrees projection angle in a specially designed device. Two types of ROI (the ruggedness of the boundary and bone profiles) were placed on each digital image. Fractal dimensions and variance in mean pixel intensity were computed from each ROI using the caliper method in ImageFractal (National Institutes of Health, Washington, DC, USA). Correlation analysis quantified the relationship between changes in variance and fractal dimensions of the two types of ROI. RESULTS: A Strong correlation (r=0.90 approximately 0.98, P</=0.0026) was found between variance in mean pixel intensity and decreasing fractal dimensions calculated from bone profiles. There was no consistency in the ruggedness of the boundary and increasing decalcification. CONCLUSIONS: The fractal dimensions used to characterize the ruggedness of a boundary of trabecular bone in a two-dimensional ROI are inadequate for the detection of osteoporosis, but those calculated from bone profiles may be a sensitive descriptor of trabecular bone structure.

Animals↗

PubMed1999

Diagnostic imaging of pigmented villonodular synovitis of the temporomandibular joint associated with condylar expansion.

Pigmented villonodular synovitis (PVNS) is a rare lesion of the temporomandibular joint. We report a case which was initially misdiagnosed as a parotid tumor. CT revealed a well-defined mass demonstrating higher attenuation than the adjacent soft tissue with marked expansion of the mandibular condyle. MRI clearly delineated the extent of the lesion which had very low signal intensity on both T1W and T2W sequences due to the effect of hemosiderin. The usefulness of these imaging procedures in diagnosis of PVNS is discussed.

Diagnosis, Differential↗

PubMed1999

Inflammatory pseudotumor of the liver in patients with recurrent pyogenic cholangitis: CT-histopathologic correlation.

PURPOSE: To correlate computed tomographic (CT) features of inflammatory pseudotumors of the liver with histopathologic results in patients with recurrent pyogenic cholangitis. MATERIALS AND METHODS: CT features of 13 cases of inflammatory hepatic pseudotumor in 10 patients with recurrent pyogenic cholangitis were reviewed. Diagnosis was made by means of surgical resection in all patients. CT scans were analyzed for the appearance of masses and ancillary findings in correlation with the histopathologic findings in each resected specimen. RESULTS: The masses were 2.0-7.0 cm (mean, 3.5 cm). At nonenhanced CT, the masses appeared as ill-defined, hypoattenuating lesions. At contrast material-enhanced CT, the masses exhibited central hypoattenuating areas with an iso- or hyperattenuating thickened periphery in four cases and a multiseptate appearance with hyperattenuating internal septa and periphery in nine cases. CT-histopathologic correlation showed that the central hypoattenuating area indicated the presence of chronic inflammatory infiltrates with foamy histiocytes, plasmacytes, and lymphocytes, while iso- or hyperattenuating areas in the periphery and internal septa of the mass represented fibroblastic proliferation. All patients had CT features of recurrent pyogenic cholangitis, such as hepatolithiasis, intrahepatic duct stricture and dilatation, common bile duct calculi, pneumobilia, or parenchymal atrophy. CONCLUSION: Although CT features are not specific, inflammatory pseudotumor should be included in the differential diagnosis in patients with recurrent pyogenic cholangitis and a hepatic mass detected at CT.

Adult↗

PubMed1999

Effects of citicoline combined with thrombolytic therapy in a rat embolic stroke model.

BACKGROUND AND PURPOSE: We sought to evaluate the effects of the combination of cytidine-5'-diphosphocholine (citicoline) and thrombolysis on infarct size, clinical outcome, and mortality in a rat embolic stroke model. METHODS: Eighty-three Sprague-Dawley rats were embolized in the carotid territory with a single fibrin embolus and randomly assigned to the following treatment groups: (1) control (saline), (2) citicoline 250 mg/kg, (3) citicoline 500 mg/kg, (4) recombinant tissue plasminogen activator (rtPA) 5 mg/kg, (5) rtPA 5 mg/kg plus citicoline 250 mg/kg, and (6) rtPA 5 mg/kg plus citicoline 500 mg/kg. rtPA was administered as a continuous intravenous infusion over 45 minutes starting 45 minutes after embolization; citicoline was given intraperitoneally 30 minutes and 24, 48, and 72 hours after embolization. At 96 hours, the brains were fixed and stained by hematoxylin-eosin, and infarct volumes were measured. Neurological scores were determined daily. RESULTS: The median infarct size, measured as percentage of the affected hemisphere, in the control group was 37% (interquartile range, 26% to 69%) compared with 22% (5% to 52%; P=NS) in group 2, 11% (5% to 34%; P=NS) in group 3, 24% (12% to 31%; P=NS) in group 4, 11% (3% to 22%; P=0.02) in the combined group 5, and 19% (9% to 51%; P=NS) in group 6. The infarct size was significantly reduced in the combined citicoline+rtPA-treated groups to a median of 13% (5% to 30%; P<0.01). Citicoline 500 mg/kg and citicoline combined with rtPA also promoted functional recovery. CONCLUSIONS: These results demonstrate that the combination of low-dose citicoline and rtPA significantly reduced infarct size in this focal ischemia model.

Animals↗

PubMed1998

Early cerebral blood volume after severe traumatic brain injury in patients with early cerebral ischemia.

Recent early cerebral blood flow (CBF) studies on severe head injury have revealed ischemia in a substantial number of patients with a variety of CT diagnoses. However, the underlying derangements causing this early ischemia are unknown, but cerebral blood volume (CBV) measurements might offer some insight into this pathology. Therefore, acute CBF and CBV measurements were performed in 51 adult severely head injured patients within 24 hours after injury. For this purpose the stable Xenon-CT procedure was used for assessment of CBF, and a dynamic CT imaging technique was used for determining CBV. All ischemic patients were found among 35 subjects studied within 4 hours after injury (31%). Based on the occurrence of regional ischemia seven patients with varying anatomical lesions on CT were selected for comparison between CBF and CBV in ischemic and non-ischemic areas. Both CBF (p < 0.02) and CBV (p < 0.02) exhibited significantly lower values in the ischemic zones. Ten patients showing a subdural hematoma (SDH) were studied preceding surgery and seven were ischemic in at least one lobe or brainstem. Ipsilateral CBF was lower than CBF in the contralateral side (p < 0.1). CBV at the ipsilateral side was significantly reduced compared to the contralateral side (p < 0.05). Follow-up studies were performed in three ischemic patients and in one borderline ischemic patient immediately after removal of SDH showing a striking increase in both CBF and CBV. In the remaining 26 subjects follow-up studies were obtained between day 2 and day 8 and all patients showed CBF values within the normal range. These data evidently support the suggestion that compromise of the microvasculature is the cause of early ischemia, rather than vasospasm of the larger conductance vessels. This has implications for acute post-traumatic therapeutical strategies and management of the severely head injured patient and may lead to testing of new drugs that are effective in interfering with processes causing this ischemia.

Adolescent↗

PubMed1998

Sample size in clinical trials with dichotomous endpoints: use of covariables.

In many clinical trials, the primary endpoint is dichotomous. In this article, we examine the possibility of reducing the required sample size by removing variation associated with baseline covariables. Three measures are used to study the size of the reduction. Simulation studies based on a database of head trauma and of stroke patients suggested that a substantial reduction in the sample size can be achieved when the correlation between the endpoint and covariables is strong. A simple ad hoc formula for approximating the required sample size is proposed.

Adult↗

PubMed1998

Effect of delayed observations on Bayesian decisions for binary data.

A Bayesian decision rule for early termination of an experimental study of binary responses is presented. This early termination occurs when the predictive probability of reversing the decision when utilizing the delayed observations is small. The proposed approach utilizes Bayesian inferential tools such as Bayes factors and predictive distributions. A simulation study is conducted to evaluate the performance of the proposed approach. Some guidelines are given to determine when the study should be terminated early and when the investigator should wait for delayed observations before making a conclusion.

Bayes Theorem↗

PubMed1998

Primary end points in phase III clinical trials of severe head trauma: DRS versus GOS. The American Brain Injury Consortium Study Group.

The most commonly used primary end point in phase III clinical trials of severe head trauma is the Glasgow Outcome Scale (GOS), usually dichotomized to favorable (good) and unfavorable (poor) outcomes. The alternative endpoints include the Disability Rating Scale (DRS) with a 31-point scale. The purpose of this study was to compare DRS and GOS using the data collected from two completed clinical trials organized by the American Brain Injury Consortium and two pharmaceutical companies. The two outcome scales were examined and compared in terms of the correlation between the two scales, sensitivity, and p values between the differences between two arms of the trials. There was no indication that the DRS was more sensitive or advantageous relative to the dichotomized or four-category GOS. In addition, the highly significant correlation between the two outcome scales (r = 0.95; p < 0.0001) could not justify the DRS as an end point. The other problems with the DRS include the difficulty of determining the clinically meaningful difference in designing trials. The study suggested that the GOS is a better primary end point than DRS.

Adult↗

PubMed1998

Regional cerebral blood volume after severe head injury in patients with regional cerebral ischemia.

OBJECTIVE: Recent early cerebral blood flow (CBF) studies in cases of severe head injury have revealed ischemia in a substantial number of patients with a variety of computed tomographically demonstrated diagnoses. The underlying derangements causing this early ischemia are unknown, but cerebral blood volume (CBV) measurements might offer some insight into this pathological abnormality. METHODS: For this purpose, stable xenon-enhanced computed tomography was used for assessment of CBF, and a dynamic computed tomographic imaging technique was used for determining CBV. Based on the occurrence of regional ischemia (CBF < 20 ml/100 g/min), seven patients with varying anatomic lesions revealed by computed tomography were identified for comparison between CBF and CBV in ischemic and nonischemic areas. RESULTS: Both CBF (15+/-4.3 versus 34+/-11 g/min, P < 0.002) and CBV (2.5+/-1.0 versus 4.9+/-1.9 ml/100 g) exhibited significantly lower values in the ischemic zones than in the nonischemic zones (means+/-standard deviations). Among 26 patients with or without ischemia observed during their initial follow-up studies, which were conducted between Days 2 and 8, all patients showed CBF and CBV values within the low-normal range. CONCLUSION: These data evidently support the suggestion that compromise of the microvasculature is the cause of early ischemia, rather than vasospasm of the larger conductance vessels.

Adolescent↗

PubMed1998

Factors affecting excitatory amino acid release following severe human head injury.

OBJECT: Recent animal studies demonstrate that excitatory amino acids (EAAs) play a major role in neuronal damage after brain trauma and ischemia. However, the role of EAAs in patients who have suffered severe head injury is not understood. Excess quantities of glutamate in the extracellular space may lead to uncontrolled shifts of sodium, potassium, and calcium, disrupting ionic homeostasis, which may lead to severe cell swelling and cell death. The authors evaluated the role of EEAs in human traumatic brain injury. METHODS: In 80 consecutive severely head injured patients, a microdialysis probe was placed into the gray matter along with a ventriculostomy catheter or an intracranial pressure (ICP) monitor for 4 days. Levels of EAAs and structural amino acids were analyzed using high-performance liquid chromatography. Multifactorial analysis of the amino acid pattern was performed and its correlations with clinical parameters and outcome were tested. The levels of EAAs were increased up to 50 times normal in 30% of the patients and were significantly correlated to levels of structural amino acids both in each patient and across the whole group (p < 0.01). Secondary ischemic brain injury and focal contusions were most strongly associated with high EAA levels (27+/-22 micromol/L). Sustained high ICP and poor outcome were significantly correlated to high levels of EAAs (glutamate > 20 micromol/L; p < 0.01). CONCLUSIONS: The release of EAAs is closely linked to the release of structural amino acids and may thus reflect nonspecific development of membrane micropores, rather than presynaptic neuronal vesicular exocytosis. The magnitude of EAA release in patients with focal contusions and ischemic events may be sufficient to exacerbate neuronal damage, and these patients may be the best candidates for treatment with glutamate antagonists in the future.

Amino Acids↗

PubMed1997

Clinical trials in traumatic brain injury. What can we learn from previous studies?

Many compounds have now been tested that were expected to ameliorate the secondary ischemic brain damage after severe head injury. Thus far, none of these have been clearly successful. This review is an attempt to identify factors that could be responsible for some of these failures. Recommendations are made that could help to avoid these pitfalls in the future. The usefulness and criteria for use of animal models for traumatic brain injury to depict human head injury are discussed. Clearly, it has now become widely accepted that mechanism-driven trials, in which individual pathophysiological mechanisms are targeted, are preferable in this heterogeneous patient population. Other factors, such as the effect of brain penetration, safety and tolerability of the compound, and the interface between the pharmaceutical industry and academics are a major influence in the success of these trials. Furthermore, different ways of analyzing trials such as sequential analysis and newer, alternative end points should be considered. Pharmacological agents will never be the "magic bullet" for a process as heterogenous in pathophysiological mechanisms as traumatic brain injury. This does not imply that the role of neuroprotective compounds will not be important in the future. New approaches in developing, conducting and analyzing these expensive clinical trials must be devised in the future.

Animals↗

PubMed1997

Bayesian approach to two-stage phase II trial.

Consider the situation in which there are several different therapeutic agents. It is desired to select the best agent and to examine its efficacy relative to the control. Too often clinical trials terminate with negative outcomes in part due to inadequate phase II studies. A two-stage phase II based on a Bayesian approach is considered in order to reduce such likelihood. The first stage consists of selecting the best agent and the second stage consists of examining the relative efficacy of the selected agent compared to the control. A formal phase III clinical trial can be initiated when the particular agent is shown to be promising on the basis of the proposed phase II study. The Bayesian approach employed uses an ad hoc likelihood due to the fact that the exact likelihood is complex and intractable. In this sense the proposed approach is thus an approximation. A simulation study is conducted to investigate the performance of the proposed Bayesian approach and compared to two fixed-sample-size approaches. Due to the fact that the procedure is approximate, the simulation study is essential to assess the usefulness of the procedure. The study suggests that the Bayesian approach is an attractive alternative to fixed-sample-size approaches.

Bayes Theorem↗

PubMed1997

Interim analyses and early termination of clinical trials.

The group sequential tests (GST) are appropriate for performing interim analyses in clinical trials. Various GST are reviewed and compared in this paper in terms of the expected sample size, the maximum sample size, and other practical aspects. Also discussed are the p-values of the significant differences for GST. Common problems and difficulties of using GST in practice are examined. One problem is difficulties associated with the delayed data accumulated after a trial is terminated at an interim test. The GST with O'Brien-Fleming type of boundaries are found to be safe in dealing with delayed observations. Possible approaches for performing futility analyses are illustrated with examples. It is recommended that futility analysis with GST be built into the design of large clinical trials.

Clinical Trials as Topic↗

PubMed1997

Continuous monitoring of cerebral substrate delivery and clearance: initial experience in 24 patients with severe acute brain injuries.

OBJECTIVE: Current neuromonitoring techniques in severe human head injury often fail to detect the causes of clinical deterioration. A sensor is now available for continuous monitoring of brain oxygen tension, carbon dioxide tension, and pH values. In this study, brain tissue oxygen tension was used to differentiate patients at risk for brain ischemia and to predict outcome. METHODS: The multiparameter sensor was inserted into brain tissue, along with a standard ventriculostomy catheter and a microdialysis probe, in 24 patients. Lactate and glucose were measured by high-pressure liquid chromatography in hourly dialysate samples. RESULTS: Patients who experienced a good recovery (n = 8) sustained a mean brain partial oxygen pressure of 39 +/- 4 mm Hg, brain partial carbon dioxide pressure (PCO2) of 50 +/- 8 mm Hg, and a brain pH of 7.14 +/- 0.12. Patients with moderate to severe disability (n = 6) sustained a mean brain partial oxygen pressure of 31 +/- 5 mm Hg, brain PCO2 of 47 +/- 2 mm Hg, and a brain pH of 7.11 +/- 0.12. Ten patients who died or remained vegetative sustained a mean brain partial oxygen pressure of 19 +/- 8 mm Hg, a brain PCO2 of 64 +/- 21 mm Hg, and a brain pH of 6.85 +/- 0.41. Mean brain PCO2 levels of 90 to 150 mm Hg were consistently observed after cerebral circulatory arrest or brain death. Dialysate lactate and glucose were less clearly correlated to outcome than brain oxygen tension. Dialysate glucose was extremely low in all patients and zero in most patients who died. CONCLUSION: Brain oxygen pressure, brain carbon dioxide pressure, and brain pH measurements, as well as a microdialysis probe for glucose and lactate analysis, may optimize the management of comatose neurosurgical patients by allowing a fuller understanding of the dynamic factors affecting brain metabolism.

Acute Disease↗

PubMed1996

Thresholds for cerebral ischemia after severe head injury: relationship with late CT findings and outcome.

Cerebral ischemic insults in at least 30% of severely head injured patients at a very early stage following trauma and are associated with early death. To date, the threshold for ischemia of 18 mL/100g/min used in human head injury studies has been adopted from animal studies (by temporary occlusion of the middle cerebral artery). Since the traumatized brain becomes more susceptible to irreversible damage if accompanied by ischemia one may question whether the threshold for ischemic vulnerability is higher than 18 mL/100 g/min. Cerebral ischemia can cause atrophy. Therefore, the authors obtained computerized tomography (CT) scans in 33 comatose head-injured patients (Glasgow Coma Score of 8 or less) at least 3 months following injury and compared ventricle sizes (as a reflection of atrophy) with cerebral blood flow (CBF) obtained within 4 h (average 2.3 +/- 0.8 h) after injury. Ventricular measurements were performed in three fashions: the third ventricular size (cm), the bicaudate cerebral ventricular index (BCVI), and the hemispheric ventricular index (HCVI). No significant correlation was found between early CBF and any of the ventricule sizes. Applying a multiple correlation analysis with four independent parameters [CBF, CBF/time postinjury, CBF/(time postinjury)2, age], only age emerged as a significant indicator for predicting ventricle size (p < 0.001). We also compared CBF data, obtained within 4 h after trauma, from survivors at 3 months after injury (mean CBF of 32 mL/100 g/min) with CBF data from non-survivors (CBF 20 mL/100 g/min). The difference in CBF between survivors and nonsurvivors was significant at p < 0.001 (Wilcoxon rank-sum test). The proportion of patients with CBF less than or equal to 20 mL/100 g/min was 56% in the nonsurvivors and only 5% in survivors. The difference in the proportions was significant at p < 0.001 (chi-square test). We conclude that a measure of atrophy does not correlate with ultra-early CBF. However, based on the clear distinction between survivors and nonsurvivors, we suggest the threshold for ischemia after head injury be redefined as a CBF of 20 mL/100 g/min.

Adolescent↗

PubMed1995

Effect of non-random missing data mechanisms in clinical trials.

A simple form of non-ignorable missing data mechanisms based on two parameters is used to characterize the amount of missing data and the severity of non-randomness in clinical trials. Based on the formulation, the effect of non-randomly missing data on simple analyses which ignore the missing data is studied for binary and normally distributed response variables. In general, the effect of the non-randomly missing data on the bias and the power increases with the severity of non-randomness. The bias can be positive or negative and the power can be less than or greater than when the data are missing at random. The results of the analysis, ignoring the missing data, can be seriously flawed if the non-randomness is severe, even when only a small proportion of the sample is missing. The problem is more pronounced in the case of normally distributed response variables with unequal variances.

Bias↗

PubMed1995

A simple measure in defining optimal strata in clinical trials.

This paper deals with balancing groups with respect to prognostic factors in clinical trials, as a means of increasing the power of a study. We use the Mantel-Haenszel statistic to obtain a simple measure for assessing the relative efficiency of different factors for stratification and to find optimal cutpoints for the given factors. For any available database, the measure can be used to construct optimal strata for a clinical trial. The paper also presents a practical approach for reducing the number of strata using discriminant regions with a method of assessing the effectiveness of this approach. An example from a large database of severe head trauma patients illustrates the utility of the measure.

Clinical Trials as Topic↗

PubMed1995

Culture, gender, and self: a perspective from individualism-collectivism research.

Individualism and collectivism are often equated with independent vs. interdependent, agentic vs. communal, and separate vs. relational self-construals. Although these same concepts have been used to characterize both cultural and gender differences, a perspective of cultural evolution suggests it is unlikely. A division of labor within society may produce gender differences, but this cannot explain cultural differences. A study of self-construal involving 5 cultures (Australia, the United States, Hawaii, Japan, and Korea) shows that differences between these cultures are captured mostly by the extent to which people see themselves as acting as independent agents, whereas gender differences are best summarized by the extent to which people regard themselves as emotionally related to others.

Adolescent↗